tbuckley/cabot-search huggingface dataset:
Exosomal-miR-129-2-3p derived from <i>Fusobacterium nucleatum</i> -infected intestinal epithelial cells promotes experimental colitis through regulating TIMELESS-mediated cellular senescence pathway
Authors: Shuchun Wei, Xiaohan Wu, Meilin Chen, Zixuan Xiang, Xiangyun Li, Jixiang Zhang, Weiguo Dong
Journal: Gut Microbes (2023)

Fusobacterium nucleatum (Fn) infection is known to exacerbate ulcerative colitis (UC). However, the link between Fn-infected intestinal epithelial cell (IEC)-derived exosomes (Fn-Exo) and UC progression has not been investigated. Differentially expressed miRNAs in Fn-Exo and non-infected IECs-derived exosomes (Con-Exo) were identified by miRNA sequencing. Then, the biological role and mechanism of Fn-Exo in UC development were determined in vitro and in vivo. We found that exosomes delivered miR-129-2-3p from Fn-infected IECs into non-infected IECs, exacerbating epithelial barrier dysfunction and experimental colitis. Mechanically, Fn-Exo induces DNA damage via the miR-129-2-3p/TIMELESS axis and subsequently activates the ATM/ATR/p53 pathway, ultimately promoting cellular senescence and colonic inflammation. In conclusion, Exo-miR-129-2-3p/TIMELESS/ATM/ATR/p53 pathway aggravates cellular senescence, barrier damage, and experimental colitis. The current study revealed a previously unknown regulatory pathway in the progression of Fn-infectious UC. Furthermore, Exosomal-miR-129-2-3p in serum and TIMELESS may function as novel potential diagnostic biomarkers for UC and Fn-high-UC.
Atezolizumab in Combination with Bevacizumab for the Management of Patients with Hepatocellular Carcinoma in the First-Line Setting: Systematic Literature Review and Meta-Analysis
Authors: Arndt Vogel, Richard S Finn, Marie-Hélène Blanchet Zumofen, Carolina Heuser, Javier Sanchez Alvarez, Michael Leibfried, Catherine R Mitchell, Sarah Batson, Gabrielle Redhead, Vincent E Gaillard, Masatoshi Kudo
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (&lt;i&gt;n&lt;/i&gt; = 1) for OS and progression-free survival (PFS). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.
Injury Site Specific Xenon Delivered by Platelet Membrane‐Mimicking Hybrid Microbubbles to Protect Against Acute Kidney Injury via Inhibition of Cellular Senescence (Adv. Healthcare Mater. 20/2023)
Authors: Jing Yang, Chaojin Chen, Xiaoyan Miao, Tienan Wang, Yu Guan, Linan Zhang, Sufang Chen, Zheng Zhang, Zhengyuan Xia, Jiayi Kang, Haobo Li, Tinghui Yin, Ziqing Hei, Weifeng Yao
Journal: Advanced Healthcare Materials (2023)

In article 2203359 Haobo Li, Tinghui Yin, Ziqing Hei, Weifeng Yao, and co-workers, Xe-Pla-MBs is injected and targeted to the damaged renal vascular endothelium with platelet-mimicking properties.The destructive pulse of the clinical ultrasound system is used to release the inner xenon gas from the Xe-Pla-MBs.Xenon enters the renal tubular epithelial cells through the temporal intercellular gap of vascular endothelial and significantly improves renal function by downregulating cellular senescent signaling.
A Non‐G‐Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer (Adv. Healthcare Mater. 20/2023)
Authors: Yunyi Liu, Bei Hu, Xiaming Pei, Juan Li, Dan Qi, Yuxi Xu, Hailong Ou, Yatao Wu, Lei Xue, Jason H. Huang, Erxi Wu, Xiaoxiao Hu
Journal: Advanced Healthcare Materials (2023)

DNA Aptamers Article 2300791 by Erxi Wu, Xiaoxiao Hu, and co-workers highlights the development of a non-G-quadruplex, nucleolin-targeting aptamer TB-5, which inhibits the invasion, migration, and proliferation of bladder cancer cells by disrupting mRNA transcription processes. TB-5 demonstrates potential as a diagnostic and therapeutic tool due to its high specificity and affinity for bladder cancer tissues, elucidating the significant role of nucleolin in bladder cancer pathology.
A Bioinspired Gelatin–Amorphous Calcium Phosphate Coating on Titanium Implant for Bone Regeneration (Adv. Healthcare Mater. 20/2023)
Authors: Yanhuizhi Feng, Di Wu, Jennifer Knaus, Sascha Keßler, Bing Ni, ZongKun Chen, Johnathan Avaro, Rui Xiong, Helmut Cölfen, Zuolin Wang
Journal: Advanced Healthcare Materials (2023)

Titanium Implants In article 2203411 by Helmut Cölfen, Zuolin Wang, and co-workers, a facile method to fabricate Gel-ACP (gelatin-amorphous calcium phosphate) coatings on titanium is demonstrated, providing a promising strategy to mimic the initial bone biological apatite and thus obtaining a rapid bone formation at the interface of bone and implant.
British Thoracic Society Guideline for diagnosing and monitoring paediatric sleep-disordered breathing
Authors: Hazel J Evans, Neil A Gibson, Joanna Bennett, Samantha YS Chan, Johanna Gavlak, Katharine Harman, Hasnaa Ismail-Koch, Ruth N Kingshott, Ross Langley, Andrew Morley, Kirstie S Opstad, Kylie Russo, Martin P Samuels, Hui Leng Tan, Daniel Tweedie, Michael Yanney, Andrea Whitney
Journal: Thorax (2023)
Complement
Authors: Paul A. Monach
Journal: Arthritis & Rheumatology (2023)

The role of complement in human autoimmune, inflammatory, and infectious diseases is reviewed, focusing on clinical applicability. A typical case is presented in which serum testing for C3 and C4 is performed to help assess a syndrome with a broad differential diagnosis. The review includes a discussion of complement deficiency states, consumption of complement by diseases characterized by immune‐complex formation and deposition, usefulness and interpretation of laboratory tests for complement, and development of drugs targeting specific components of the complement pathway for a growing number of indications.
Beyond matrix stiffness: targeting force-induced cancer drug resistance
Authors: Maria Kalli, Matthew D. Poskus, Triantafyllos Stylianopoulos, Ioannis K. Zervantonakis
Journal: Trends in cancer (2023)

During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in tumor growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies and mechanotransduction programs that regulate cellular processes, including cell proliferation, apoptosis, survival and phenotype switching. We discuss how the therapeutic response is impacted by the three main mechanical TME abnormalities: high extracellular matrix (ECM) composition and stiffness; interstitial fluid pressure (IFP); and elevated mechanical forces. We also review drugs that normalize these abnormalities or block mechanosensors and mechanotransduction pathways. Finally, we discuss current challenges and perspectives for the development of new strategies targeting mechanically induced drug resistance in the clinic.
Unusual Surface Coagulation Activation Patterns of Crystalline and Amorphous Silicate‐Based Biominerals (Adv. Healthcare Mater. 20/2023)
Authors: Chunyu Liu, Xu Cui, Yunbo Du, Xue Wang, Jua Kim, Shuaijie Li, Liyan Zhang, Xiaoli Zhao, Limin Zhao, Pengfei Tian, Hao Zhang, Kun Su, Xian Li, Haobo Pan
Journal: Advanced Healthcare Materials (2023)
Transformative Medical Materials (Adv. Healthcare Mater. 20/2023)
Authors: Laura De Laporte, Fabian Kiessling
Journal: Advanced Healthcare Materials (2023)

Transformative Medical Materials In the special section of this issue, centered on transformative medical materials, and presented in the guest editorial 2301637 by Laura De Laporte and Fabian Kiessling, several colleagues of RWTH Aachen University in Germany join their expertise to cover the potential of transformative materials in four focus areas and presented in four perspective articles: in vitro human tissue models, in vivo regeneration, biontronics, and drug delivery systems. This type of materials can adapt to and interact with human cells and tissues and respond on-demand to internal and external triggers, to better mimic tissue structures and fully integrate into the body to restore function.
Exploring the interplay of gout, genetic factors, and dietary influences: comment on the article by Lin et al
Authors: Wei‐Chiao Kao, Po‐Cheng Shih, James Cheng‐Chung Wei
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CDK7 and CDK9 inhibition interferes with transcription, translation, and stemness, and induces cytotoxicity in GBM irrespective of temozolomide sensitivity
Authors: Isha Bhutada, Fatema Khambati, Shi-Yuan Cheng, Deanna M Tiek, Derek Duckett, Harshani Lawrence, Michael A Vogelbaum, Qianxing Mo, Srikumar P Chellappan, Jaya Padmanabhan
Journal: Neuro-Oncology (2023)

Abstract Background Glioblastoma (GBM) is refractory to current treatment modalities while side effects of treatments result in neurotoxicity and cognitive impairment. Here we test the hypothesis that inhibiting CDK7 or CDK9 would effectively combat GBM with reduced neurotoxicity. Methods We examined the effect of a CDK7 inhibitor, THZ1, and multiple CDK9 inhibitors (SNS032, AZD4573, NVP2, and JSH150) on GBM cell lines, patient-derived temozolomide (TMZ)-resistant and responsive primary tumor cells and glioma stem cells (GSCs). Biochemical changes were assessed by western blotting, immunofluorescence, multispectral imaging, and RT-PCR. In vivo, efficacy was assessed in orthotopic and subcutaneous xenograft models. Results CDK7 and CDK9 inhibitors suppressed the viability of TMZ-responsive and resistant GBM cells and GSCs at low nanomolar concentrations, with limited cytotoxic effects in vivo. The inhibitors abrogated RNA Pol II and p70S6K phosphorylation and nascent protein synthesis. Furthermore, the self-renewal of GSCs was significantly reduced with a corresponding reduction in Sox2 and Sox9 levels. Analysis of TCGA data showed increased expression of CDK7, CDK9, SOX2, SOX9, and RPS6KB1 in GBM; supporting this, multispectral imaging of a TMA revealed increased levels of CDK9, Sox2, Sox9, phospho-S6, and phospho-p70S6K in GBM compared to normal brains. RNA-Seq results suggested that inhibitors suppressed tumor-promoting genes while inducing tumor-suppressive genes. Furthermore, the studies conducted on subcutaneous and orthotopic GBM tumor xenograft models showed that administration of CDK9 inhibitors markedly suppressed tumor growth in vivo. Conclusions Our results suggest that CDK7 and CDK9 targeted therapies may be effective against TMZ-sensitive and resistant GBM.
Immunoreactivity of HOXB13 in Neuroendocrine Neoplasms Is a Sensitive and Specific Marker of Rectal Well-Differentiated Neuroendocrine Tumors
Authors: Jiri Soukup, Monika Manethova, Vaclav Stejskal, Helena Hornychova, Tomas Cesak, David Netuka, Ales Ryska, Filip Gabalec
Journal: Endocrine Pathology (2023)
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with <i>COL15A1</i>-Positive Endothelial Cells
Authors: Jonas C. Schupp, Edward P. Manning, Maurizio Chioccioli, Jan C. Kamp, Leonard Christian, Changwan Ryu, Erica Herzog, Mark P. Kühnel, Antje Prasse, Naftali Kaminski, Danny D. Jonigk, Robert J. Homer, Lavinia Neubert, Fabio Ius, Aurélien stringJustet, Lida P. Hariri, Benjamin Seeliger, Tobias Welte, Rachel S. Knipe, Jens Gottlieb
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1 Positive Endothelial Cells." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
S113: IMPACT OF IKZF1 DELETION IN RELAPSED AND/OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH CD19-CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY
Authors: Zihong Cai, Ting Zhang, Suning Chen, Liang Huang, Qifa Liu, Hongsheng Zhou
Journal: HemaSphere (2023)

Background: Although CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) has emerged as one of the promising therapeutic approaches to relapsed and/or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), more than half of recipients will ultimately experience disease progression. Mounting evidence shows that resistance to CAR-T therapy influenced by the factors not only related to effector cells, but target cells. Previous studies have shown the poor outcome conferred by IKZF1 deletions, but have not been explored in the context of CAR T-cell therapy. Therefore, it is necessary to explore the impact of IKZF1 deletion on the prognostic value of patients receiving CAR-T therapy. Aims: We determined to assess the prognostic effect of IKZF1 deletion to CAR-T therapy, explore the mechanism of resistance, and develop a potential therapeutic strategy for these patients. Methods: Here we enrolled two cohorts to analyze the impact of IKZF1 deletion. The first cohort included 129 patients receiving CAR-T therapy from three centers. After that, a IKZF1 deletion cohort of 113 patients was establish to analyze whether CAR T therapy can overcome genetic adverse features, IKZF1 deletion, to induce remission. Results: Within the CAR-T cohort, the inferior EFS of enrolled patients was observed in IKZF1 deletion group (P=0.041, Fig.A). In a multivariable Cox regression model adjusting for factors contributing to event-free survival, including Ph status, immunophenotype, and chromosome karyotype, IKZF1 deletion remained independently associated with inferior event-free survival (P=0.025, Fig.B). In the cohort of patients with IKZF1 deletion, EFS rates of CAR-T group were comparable with the no-CAR-T group (Fig.C). CAR-T therapy cannot abrogate the dismal survival of patients with IKZF1 deletion in the multivariable regression models (P=0.157, Fig.D). Summary/Conclusion: IKZF1 deletion is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with B-ALL treated with CD19-CAR-T. Further mechanisms are needed to explore how tumor intrinsic phenotype promote resistance to the antitumor immune response, and could represent targets to potentiate the efficacy of CAR-T therapy.Keywords: CAR-T, Adult, Acute lymphoblastic leukemia
Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study
Authors: Emilie Helte, Melle Säve-Söderbergh, Susanna C Larsson, Anna Martling, Agneta Åkesson
Journal: JNCI Journal of the National Cancer Institute (2023)

Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive.
Review of Prediabetes
Authors: Mayer B. Davidson
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Whole-genome sequencing across 449 samples spanning 47 ethnolinguistic groups provides insights into genetic diversity in Nigeria
Authors: Esha Joshi, Arjun Biddanda, Jumi Popoola, Aminu Yakubu, Oluyemisi Osakwe, Delali Attipoe, Estelle Dogbo, Babatunde Salako, Oyekanmi Nash, Omolola Salako, Olubukunola Oyedele, Golibe Eze-Echesi, Segun Fatumo, Abasi Ene-Obong, Colm O'Dushlaine
Journal: Cell Genomics (2023)

African populations have been drastically underrepresented in genomics research, and failure to capture the genetic diversity across the numerous ethnolinguistic groups (ELGs) found on the continent has hindered the equity of precision medicine initiatives globally. Here, we describe the whole-genome sequencing of 449 Nigerian individuals across 47 unique self-reported ELGs. Population structure analysis reveals genetic differentiation among our ELGs, consistent with previous findings. From the 36 million SNPs and insertions or deletions (indels) discovered in our dataset, we provide a high-level catalog of both novel and medically relevant variation present across the ELGs. These results emphasize the value of this resource for genomics research, with added granularity by representing multiple ELGs from Nigeria. Our results also underscore the potential of using these cohorts with larger sample sizes to improve our understanding of human ancestry and health in Africa.
Review of Prediabetes
Authors: Taher Entezari-Maleki
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cervical Cancer Screening
Authors: Rebecca B. Perkins, Nicolas Wentzensen, Richard S. Guido, Mark Schiffman
Journal: JAMA (2023)

Each year in the US, approximately 100 000 people are treated for cervical precancer, 14 000 people are diagnosed with cervical cancer, and 4000 die of cervical cancer.Essentially all cervical cancers worldwide are caused by persistent infections with one of 13 carcinogenic human papillomavirus (HPV) genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. HPV vaccination at ages 9 through 12 years will likely prevent more than 90% of cervical precancers and cancers. In people with a cervix aged 21 through 65 years, cervical cancer is prevented by screening for and treating cervical precancer, defined as high-grade squamous intraepithelial lesions of the cervix. High-grade lesions can progress to cervical cancer if not treated. Cervicovaginal HPV testing is 90% sensitive for detecting precancer. In the general population, the risk of precancer is less than 0.15% over 5 years following a negative HPV test result. Among people with a positive HPV test result, a combination of HPV genotyping and cervical cytology (Papanicolaou testing) can identify the risk of precancer. For people with current precancer risks of less than 4%, repeat HPV testing is recommended in 1, 3, or 5 years depending on 5-year precancer risk. For people with current precancer risks of 4% through 24%, such as those with low-grade cytology test results (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) and a positive HPV test of unknown duration, colposcopy is recommended. For patients with precancer risks of less than 25% (eg, cervical intraepithelial neoplasia grade 1 [CIN1] or histologic LSIL), treatment-related adverse effects, including possible association with preterm labor, can be reduced by repeating colposcopy to monitor for precancer and avoiding excisional treatment. For patients with current precancer risks of 25% through 59% (eg, high-grade cytology results of ASC cannot exclude high-grade lesion [ASC-H] or high-grade squamous intraepithelial lesion [HSIL] with positive HPV test results), management consists of colposcopy with biopsy or excisional treatment. For those with current precancer risks of 60% or more, such as patients with HPV-16-positive HSIL, proceeding directly to excisional treatment is preferred, but performing a colposcopy first to confirm the need for excisional treatment is acceptable. Clinical decision support tools can facilitate correct management.Approximately 100 000 people are treated for cervical precancer each year in the US to prevent cervical cancer. People with a cervix should be screened with HPV testing, and if HPV-positive, genotyping and cytology testing should be performed to assess the risk of cervical precancer and determine the need for colposcopy or treatment. HPV vaccination in adolescence will likely prevent more than 90% of cervical precancers and cancers.